Hepatocellular carcinoma (HCC) is a major cause of death in Taiwan as well as in Far East and some African countries. Through epidemiology studies, the most important risk factor of HCC has been shown to be HBV infection (for a review, see Chen, 1993). Great stride has been made recently in our country in preventing HBV infection and childhood HCC by implementing a HBV vaccination program (Chang, et al., 1997). Nevertheless, HCC remains a serious problem and HCC due to HCV infection still accounts for nearly 20% of the HCC cases. In the past few years, we have become interested in the genetic alterations that contributed to HCC pathogenesis. Our focus has been to identify molecular events associated with HCC development.

We began by systematically analyzing gene expressed in normal liver, HCC, and HCC cell lines. Several approaches have been taken. First, we analyzed expression of members of the protein kinase gene family or the Krupple type Zn-finger gene family. Next, we constructed cDNA libraries for normal liver and HCC and collected ESTs from these libraries. In addition, we collaborated with Chi-Hung Lin (林奇宏) and applied comparative genome hybridization (CGH) to analyze more than 70 cases of HCC samples. The results of this global analysis of HCC genomic make-up (Chen, et al., submitted) identified hot spots for gene amplification in chromosome 1q, 6p, 8q, 11q, and 17q. Moreover, frequent losses of genetic materials were observed in chromosome 4q, 8p, 13q, and 16q. We became attracted by the fact that the detected changes in 4q and 16q are consistent with the results revealed by the "loss of heterozygosity" (LOH) study, reported by many groups (for a review, see Yeh, 1998). To take a more directed approach to explore these regions, we began collaborating with Pei-Jer Chen (陳培哲) to isolate BAC clones for the HCC chromosome 4q and 16q critical regions. Since chromosome 16 is well mapped, we primarily focused on the chromosomal 4q region, in the genetic interval between D4S1544 and D4S1564. Our sequenicng effort on chromosome 16q is limited to a region (D16S3031-D16S3095) that is rich in cadherin gene family members.

• Chang, M. H., et al. (1997) Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N. Engl. J. Med. 336: 1855-1859.

• Chen, D. S. (1993) From hepatitis to hepatoma: lessons from type B hepatitis. Science. 262: 369-370.

• Chen, Y.-J., Yeh, S.-H., Chen, J.-T., Wu, C.-C., Hsu, M.-T., Tsai, S.-F., Chen, P.-J., & Lin, C.-H. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma. (2000) Gestroenterology 119: 431-440.